Monday, June 30, 2008

Turmeric, an Asian spice found in many curries, has a long history of use in reducing inflammation, healing wounds and relieving pain, but can it prevent diabetes? Since inflammation plays a big role in many diseases and is believed to be involved in onset of both obesity and Type 2 diabetes, Drew Tortoriello, M.D., an endocrinologist and research scientist at the Naomi Berrie Diabetes Center at Columbia University Medical Center, and his colleagues were curious what effect the herb might have on diabetic mice.

Dr. Tortoriello, working with pediatric resident Stuart Weisberg, M.D., Ph.D., and Rudolph Leibel, M.D., fellow endocrinologist and the co-director of the Naomi Berrie Diabetes Center, discovered that turmeric-treated mice were less susceptible to developing Type 2 diabetes, based on their blood glucose levels, and glucose and insulin tolerance tests. They also discovered that turmeric-fed obese mice showed significantly reduced inflammation in fat tissue and liver compared to controls. They speculate that curcumin, the anti-inflammatory, anti-oxidant ingredient in turmeric, lessens insulin resistance and prevents Type 2 diabetes in these mouse models by dampening the inflammatory response provoked by obesity.

Their findings are the subject of a soon-to-be published paper in Endocrinology and were presented at ENDO 2008, the Endocrine Society's annual meeting in San Francisco this week.

Turmeric (Curcuma longa) has no known dose-limiting toxicities in doses of up to at least 12 grams daily in humans. The researchers tested high-doses of a dietary curcumin in two distinct mouse models of obesity and Type 2 diabetes: high-fat-diet-fed male mice and leptin-deficient obese female mice, with lean wild-type mice that were fed low-fat diets used as controls.

The inflammation associated with obesity was shown several years ago by researchers in the Naomi Berrie Diabetes Center to be due in part to the presence of immune cells called macrophages in fat tissues throughout the body. These cells produce "cytokine" molecules that can cause inflammation in organs such as the heart, and islets of the pancreas, while also increasing insulin resistance in muscle and liver. Researchers hypothesized that by suppressing the number and activity of these cells, with turmeric or a drug with similar actions, it may be possible to reduce some of the adverse consequences of obesity.

Curcumin administration was also associated with a small but significant decline in body weight and fat content, despite level or higher calorie consumption, suggesting that curcumin beneficially influences body composition.

"It's too early to tell whether increasing dietary curcumin [through turmeric] intake in obese people with diabetes will show a similar benefit," Dr. Tortoriello said. "Although the daily intake of curcumin one might have to consume as a primary diabetes treatment is likely impractical, it is entirely possible that lower dosages of curcumin could nicely complement our traditional therapies as a natural and safe treatment."

For now, the conclusion that Dr. Tortoriello and his colleagues have reached is that turmeric – and its active anti-oxidant ingredient, curcumin – reverses many of the inflammatory and metabolic problems associated with obesity and improves blood-sugar control in mouse models of Type 2 diabetes.

In addition to exploring novel methods of curcumin administration to increase its absorption, they are also interested in identifying novel anti-inflammatory processes invoked by curcumin and in adapting those processes in the development of more potent curcumin analogues.

What makes a pointer point, a sheep dog herd, and a retriever retrieve? Why do Yorkshire terriers live longer than Great Danes? And how can a tiny Chihuahua possibly be related to a Great Dane?

Dogs vary in size, shape, color, coat length and behavior more than any other animal and until now, this variance has largely been unexplained. Now, scientists have developed a method to identify the genetic basis for this diversity that may have far-reaching benefits for dogs and their owners.

In the cover story of tomorrow's edition of the science journal Genetics, research reveals locations in a dog's DNA that contain genes that scientists believe contribute to differences in body and skull shape, weight, fur color and length – and possibly even behavior, trainability and longevity.

"This exciting breakthrough, made possible by working with leaders in canine genetics, is helping us piece together the canine genome puzzle which will ultimately translate into potential benefit for dogs and their owners," said study co-author Paul G. Jones, PhD, a Mars Veterinary™ genetics researcher at the Waltham® Centre for Pet Nutrition – part of Mars® Incorporated, a world leader in pet care that has been studying canine genetic science for the past eight years. "By applying this research approach, we may be able to decipher how genes contribute to physical or behavioral traits that affect many breeds."

Dogs originally derived from the wolf more than 15,000 years ago – a blink of the eye in evolutionary terms. Selective breeding produced dogs with physical and behavioral traits that were well suited to the needs or desires of their human owners, such as herding or hunting ability, coat color and body and skull shape and size. This resulted in the massive variance seen among the more than 350 distinct breeds that make up today's dog population. Until now, the genetic drivers of this diversity have intrigued scientists who have been trying to explain how and why the difference in physical and behavioral traits in dogs changed so rapidly from its wolf origins.

An international team of researchers, which included scientists at the National Human Genome Research Institute, the University of Utah, Sundowners Kennels in Gilroy, California and Mars' Waltham Center for Pet Nutrition in the United Kingdom, studied simple genetic markers known as Single Nucleotide Polymorphisms, or SNPs, to find places in the dog genome that correlate with breed traits. Because many traits are "stereotyped" – or fixed within breeds – researchers can zero in on these "hot spots" to see what specific genes are in the area that might contribute to differences in traits.

The research used 13,000 dog DNA samples provided by Mars Veterinary, which holds one of the most comprehensive canine DNA banks in the world. This collection has been built up with the help of pet owners who have consented to their pets providing cheek swabs and blood samples for the database. Mars' DNA bank allowed the study to cover most of the American Kennel Club recognized breeds that span a wide variety of physical and behavioral traits and differences in longevity.

"With further refinement and additional data, this method could be used to tailor products that may benefit the health of pets," Jones said. "Pet owners and veterinarians may be able to develop better care regimes based on this knowledge. In addition, genetic information about behavioral traits, such as trainability and temperament, could also help veterinarians identify the most lifestyle-appropriate pet for an owner."

This research may also have implications for human health, as dogs suffer from many of the same diseases that we do.

Sunday, June 29, 2008

Nitric oxide has emerged as an important signaling molecule in plants - as in mammals including people. In studies of a tropical medicinal herb as a model plant, researchers have found that nitric oxide targets a number of proteins and enzymes in plants.

In collaborative work with the research group of Renu Deswal, a faculty member, and her doctoral student at the Botany Department, University of Delhi, India, Agricultural Research Service (ARS) scientist Autar Mattoo has identified 19 such targeted proteins and enzymes in Kalanchoe pinnata, also known as "miracle leaf"

These proteins and enzymes are involved in regulating processes from seed germination to cell development to plant death. Notably, they also regulate many other important processes including photosynthesis, sugar metabolism, disease- and stress tolerance in plants.

Mattoo is a plant physiologist with the ARS Sustainable Agricultural Systems Laboratory at Beltsville, Md.

The collaborative research suggests that the effects of nitric oxide, a sometimes toxic byproduct of nitrogen oxidation in soil, may have broader implications in plant processes than realized. Its modification of proteins, a process called S-nitrosylation, is increasingly recognized as an ubiquitous regulatory reaction in plants and mammals.

Mattoo and Deswal have shown for the first time that nitric oxide inactivates Rubisco, a major enzyme involved in carbon dioxide fixation and photosynthesis in plants.

Kalanchoe represents plants that have a unique method of carbon dioxide fixation that is shared by succulent plants. Kalanchoe has diverse possible medicinal benefits suggesting the presence of interesting processes at work. Mattoo hopes to do similar studies with major crops grown in different production systems, with an eye toward improving both crop yields and quality, including nutritional benefits.

Other scientists have studied nitric oxide targets in the most common model plant, Arabidopsis. Mattoo and collaborators found that Kalanchoe had some nitric oxide targets in common with Arabidopsis, such as Rubisco and drought-protective proteins. They also found new protein targets in Kalanchoe that have not been reported previously.

Discoveries by Indiana University School of Medicine scientists have opened a promising door to new drugs for toxoplasmosis and other parasites that now can evade treatments by turning dormant in the body.

Their findings help explain how the parasite that causes toxoplasmosis transforms into a cyst form that resists drugs and the body's immune system, yet can emerge from its dormant state to strike when a patient's immune system is weakened.

Led by William J. Sullivan Jr., Ph.D., assistant professor of pharmacology and toxicology, and Ronald C. Wek, Ph.D., professor of biochemistry and molecular biology, the research team found a cellular signaling system that takes hold when the parasite is stressed, enabling it to transform into the cyst surrounded by a protective barrier.

The signaling system identified by the IU team could serve as a target to block the transformation into the cyst form or to attack the parasite while in the cyst form. Their report was published in the June 13 issue of the Journal of Biological Chemistry.

The Toxoplasma gondii parasite converts from an active state to the inactive cyst state when it is stressed, for example, by heat from fever. Stress response mechanisms have been well studied in yeast and other organisms, but the pathways used by the toxoplasmosis parasite had not been determined.

"We found a cellular signal that appears to put the parasite to sleep, which in turn tells us something new about how opportunistic pathogens such as Toxoplasma awaken to cause disease during immunosuppression," said Dr. Sullivan.

An estimated 60 million people in the United States are infected with the toxoplasmosis parasite, but for most infection produces flu-like symptoms or no symptoms at all. However, for people with immune system problems -- such as those undergoing chemotherapy or people with AIDS -- the disease can cause serious effects including lung problems, blurred vision and seizures. Also, infants born to mothers who are infected during or shortly before pregnancy are at risk for severe complications, miscarriages or stillbirths.

Medications to treat Toxoplasma gondii are effective but too toxic for extended use, and they don't affect the cyst form, said Dr. Sullivan.

"A healthy immune system can keep this parasite in the cyst state. Without a healthy immune system, this organism can run rampant," said Dr. Sullivan. "This can be a very serious problem for people with AIDS."

The discovery linking this stress-response mechanism to cyst formation and maintenance not only offers a possible target for new drugs, but it could also lead to a preventative vaccine -- for animals.

The Toxoplasma gondii parasite can infect most animals and birds, but it reproduces in cats, which can shed the parasite in their feces. Humans can be infected through contact with the infected feces or litter. People can also become infected by consuming undercooked meat.

A vaccine to prevent infection in cats and livestock could prevent a significant proportion of human infections, Dr. Sullivan said.

The research of Drs. Sullivan and Wek is supported by the National Institutes of Health and the American Heart Association.

Prior to the federal Clean Air Act, unhindered industrial emissions were released into the air throughout the Midwestern and Eastern United States for decades. Many of those harmful chemicals came right back down to earth in the form of acid rain, a chemical concoction that includes nitric and sulfuric acid.

Researchers have long known that acid rain can severely decrease the diversity of plant and animal communities in fresh water lakes and ponds. However, little is known about how microscopic bacteria, which form the foundation of freshwater ecosystems, respond to acidification.

To address this knowledge gap, researchers at the Darrin Fresh Water Institute of Rensselaer Polytechnic Institute have developed one of the most comprehensive databases in existence on the impacts of acid rain at the foundation of the biological community.

The team found a general link between increased acidity and decreased bacterial diversity, but surprisingly, most of the dominant species of bacteria were not directly impacted by acidification. However, some rarer types of bacterial populations were significantly or strongly correlated to acidity, rising and falling with fluctuations in water pH. The findings could eventually allow scientists to use these bacteria as indicators of lake recovery, according to Sandra Nierzwicki-Bauer, director of the Darrin Fresh Water Institute and professor of biology.

The research is part of a much broader study on how Adirondack lakes are recovering from the impacts of acidification. "Thanks in large part to the federal Clean Air Act and increased state focus on improving air quality here in New York, we are seeing a number of these lakes on a trajectory to recovery, but up until now we have had little understanding of the changing biodiversity of microbial communities within the impacted lakes as they recover," Nierzwicki-Bauer said. "I hope this study will help other scientists expand on the research and use this data to uncover additional information on how acid-impacted lakes and their ecosystems are recovering and how we can hasten that process."

The study was published in a recent edition of the journal Applied and Environmental Microbiology and was undertaken in partnership with the Skidaway Institute of Oceanography. The study is part of what has been a 12-year analysis on the recovery of Adirondack lakes from the effects of acid rain funded by the U.S. Environmental Protection Agency's Adirondack Effects Assessment Program (AEAP). The study included bacterial samples from 18 lakes, ponds, and reservoirs in various stages of recovery from acidification in the Adirondack mountain region of New York state.

For the current study, 31 physical and chemical parameters were examined for each water body, ranging from water clarity and temperature to aluminum and hydraulic retention time for a one-year period. Clone "libraries" representing the bacteria were developed from the lake samples and analyzed. The researchers found that the species diversity in acid-impacted Adirondack lakes were similar to bacterial communities in other, non-impacted freshwater systems

The impacts of acidity on most types of bacteria, including the freshwater classes of Actinobacteria and Betaproteobacteria, were found to be indirect, and population levels appeared more directly linked to a combination of acidity along with other environmental factors such as lake depth and carbon content. Several less abundant types of bacteria, including a species known as Alphaproteobacteria, were strongly correlated to acidity and might someday be used as indicators of lake recovery from acidification, according to Nierzwicki-Bauer.

The researchers are in the process of expanding their study to include an additional 13 Adirondack lakes. They also plan to further investigate the role of specific types of bacteria in the ecosystem to better understand why certain bacteria are so directly impacted by acidity while others appear relatively unaffected.

Cells with irreparable DNA damage normally induce programmed cell death, or apoptosis. However, this mechanism often fails in tumor cells so that transformed cells are able to multiply and spread throughout the body. Scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now discovered a possible cause of this failure. Tumor cells simply degrade a protein that triggers apoptosis in the case of DNA damage. Blocking this protein degradation might set apoptosis back in operation and, thus, increase the effectiveness of radiotherapy or chemotherapy. The researchers have now published their results in Nature Cell Biology.

Human Tumor Cells

Green fluorescent human breast cancer cells

Proteins that trigger programmed cell death, or apoptosis, must be kept under careful control. After all, a cell should induce its own death only if its genetic material is damaged so severely that there is a danger of its transformation into a malignantly growing tumor cell. However, minor damages in the DNA can be corrected by the cell's special repair mechanisms – hence, no reason to commit suicide!

Among the proteins that trigger apoptosis after severe DNA damage is the HIPK2 molecule. Scientists in Dr. Thomas Hofmann's research group at the German Cancer Research Center (DKFZ) have now shown that although HIPK2 is continuously produced in healthy cells, it is instantly degraded again. An enzyme called Siah-1 attaches labels to HIPK2 marking it as "garbage". Thus, the cell prevents that apoptosis is induced "accidentally".

Slightly damaged cells enter a kind of alarm status: They block degradation of HIPK2 by Siah-1 for a short time. But as soon as the damage is repaired, the cell immediately resumes labeling HIPK2 as garbage and degrades the molecule. Only in severely damaged cells, such as by a broken DNA double strand, degradation of HIPK2 by the Siah-1 enzyme is blocked permanently. As a result, HIPK2 accumulates, apoptosis is triggered, and the cell commits suicide.

Researchers assume that this could be one of the reasons why radiation therapy or chemotherapy is sometimes ineffective. Both treatment methods cause severe damage to tumor cells, which eventually leads to programmed cell death. "If resistances occur, this is often caused by tumor cells 'refusing' to take the order to commit suicide," Thomas Hofmann explains.

To prevent HIPK2 degradation, Hoffmann and his colleagues conducted experiments in which they blocked the Siah-1 enzyme. As a result, HIPK2 was able to accumulate even in cells that were only slightly damaged, and apoptosis was induced. "Cancer medicine might be able to make use of our discovery," speculates Hofmann. "For example, we could use a Siah-1 blocker simultaneously with chemotherapy or radiotherapy to get the cells back into the apoptosis program."

Scientists at the University of Liverpool are investigating how a Madagascan plant could be used to help produce crops in harsh environmental conditions.

The plant, Kalanchoe fedtschenkoi, is unique because, unlike normal plants, it captures most of its carbon dioxide at night when the air is cooler and more humid, making it 10 times more water-efficient than major crops such as wheat. Scientists will use the latest next-generation DNA sequencing to analyse the plant’s genetic code and understand how these plants function at night.

The project will generate a genome sequence database that will be used as an Internet resource for plant biologists throughout the world.

The research comes at a time when farmland across the globe normally used for growing food such as rice and wheat is being taken over by bio-fuel crops used for bioethanol production as a petrol substitute. Scientists believe that the novel genes found in Kalanchoe could provide a model of how bio-fuel plants could be grown on un-utilised desert and semi-arid lands, rather than on fertile farmland needed for producing food.

Biological scientist, Dr James Hartwell, said: “There is a lot of concern over food shortage at the moment, with more farmland being commandeered for bio-fuels. As a result of changes in our climate the Intergovernmental Panel on Climate Change has predicted a large expansion of arid regions so there is an increasing need for new crop varieties that can be productive in deserts.

“Kalanchoe is a good example of how plants can flourish in harsh environments. If we can understand how it is able to photosynthesise using much less water than current crops, we may be able to use its genetic code to develop a crop able to withstand harsh environmental conditions. It is essential that farmland be returned to food production.”

The genetic code of the plant will be deciphered using a DNA sequencing machine that uses an enzyme found in fireflies as a flash light to help read the DNA strand.

Liverpool is one of only two universities in the UK with the technology, which can read up to half a billion DNA letters in a few hours compared to more widely used technology that can only process 50,000.

The project is funded by the Biotechnology and Biological Sciences Research Council (BBSRC).

More than 15 years ago scientists discovered a way to stop a particular gene in its tracks. The Nobel Prize-winning finding holds tantalizing promise for medical science, but so far it has been difficult to apply the technique, known as RNA interference, in living cells.

Each of these jars contains the same substance.The difference is the size of the particles. Quantum dots, suspended in liquid,absorb white light and then reemit it in a specific color that depends on the particle's size.Each quantum dot is about one ten-millionth of an inch in diameterand is composed of a few hundred atoms of material. Credit: Xiaohu Gao, University of Washington

Now scientists at the University of Washington in Seattle and Emory University in Atlanta have succeeded in using nanotechnology known as quantum dots to address this problem. Their technique is 10 to 20 times more effective than existing methods for injecting the gene-silencing tools, known as siRNA, into cells.

"We believe this is going to make a very important impact to the field of siRNA delivery," said Xiaohu Gao, a UW assistant professor of bioengineering and co-author of a study published online this week in the Journal of the American Chemical Society.

"This work helps to overcome the longstanding barrier in the siRNA field: How to achieve high silencing efficiency with low toxicity," said co-author Shuming Nie, a professor in the Wallace H. Coulter Department of Biomedical Engineering, jointly affiliated with the Georgia Institute of Technology and Emory University.

Other co-authors are Maksym Yezhelyev and Ruth O'Regan at Emory and Lifeng Qi at the UW.

Short pieces of RNA, the working copy of DNA, can disable production of a protein by silencing, or deactivating, a stretch of genetic code. Research laboratories regularly use the technique to figure out what a particular gene does. In the body, RNA interference could be used to treat conditions ranging from breast cancer to deteriorating eyesight.

The recent experiments used quantum dots, fluorescent balls of semiconductor material just six nanometers across (lining up 9,000 dots end to end would equal the width of a human hair). Quantum dots' unique optical properties cause them to emit light of different colors depending on their size. The dots are being developed for cellular imaging, solar cells and light-emitting diodes.

This paper describes one of the first applications of quantum dots to drug delivery.

Each quantum dot was surrounded by a proton sponge that carried a positive charge. Without any quantum dots attached, the siRNA's negative charge would prevent it from penetrating a cell's wall. With the quantum-dot chaperone, the more weakly charged siRNA complex crosses the cellular wall, escapes from the endosome (a fatty bubble that surrounds incoming material) and accumulates in the cellular fluid, where it can do its work disrupting protein manufacture.

Key to the newly published approach is that researchers can adjust the chemical makeup of the quantum dot's proton-sponge coating, allowing the scientists to precisely control how tightly the dots attach to the siRNA.

Quantum dots were dramatically better than existing techniques at stopping gene activity. In experiments, a cell's production of a test protein dropped to 2 percent when siRNA was delivered with quantum dots. By contrast, the test protein was produced at 13 percent to 51 percent of normal levels when the siRNA was delivered with one of three commercial reagents, or reaction-causing substances, now commonly used in laboratories.

Central to the finding is that fluorescent quantum dots allow scientists to watch the siRNA's movements. Previous siRNA trackers gave off light for less than a minute, while quantum dots, developed for imaging, emit light for hours at a time. In the experiments the authors were able to watch the process for many hours to track the gene-silencer's path.

The new approach is also five to 10 times less toxic to the cell than existing chemicals, meaning the quantum dot chaperones are less likely to harm cells. The ideal delivery vehicle would have no effect; the only biological change would be siRNA blocking cells' production of an unwanted protein.

The exact reason that the quantum dots were more effective than previous techniques is, however, still a mystery.

"We believe the improvement is caused by the endosome escape, and the ability of the quantum dots to separate from the siRNA," Gao said.

Quantum dots are not yet approved for use in humans. The authors are now transferring their techniques to particles of iron oxide, several types of which have been approved by the Food and Drug Administration for use in humans. They are also working to target cancer cells by attaching to specific markers on the cells' surface. "Looking forward, this work will have important implications in in-vivo siRNA therapeutics, which will require the use of nontoxic iron oxide and biodegradable polymeric carriers rather than quantum dots," Nie said.

Friday, June 27, 2008

The bones of a 40-foot crocodile that dined on dinosaurs and 12-foot-long fish have been discovered by researchers at Yale and at the University of Chicago in the Cretaceous rocks in Niger, Africa.

The crocodile weighed about 16,000 pounds and is called Sarcosuchus imperator. It was first described about 30 years ago by a French team, which found a partial skull. Since that initial discovery, virtually nothing had been done with the species until fieldwork by researchers in 1997 and 2000 produced three adult skulls measuring almost six feet long, three juvenile skulls and some associated postcranial or body skeletal elements.

The team consisted of Hans Larsson, now a postdoctoral fellow in Yale University's Department of Ecology and Evolutionary Biology, formerly of the University of Chicago; his graduate advisor Paul Sereno of the University of Chicago and others. Their results will be published online by the journal Science at the Science Express website on October 25 at 2 p.m. See http://www.sciencexpress.org

"The juvenile skulls are between three and four feet long, if you can call that juvenile," said Larsson. "Our calculations in the Science paper estimate the total adult body length to be between 39 and 42 feet long, probably the largest crocodile known so far."

The team sectioned the bony plates in the skin called scutes and found that the animals lived for about 42 years before reaching the large adult size. They estimate that the large adults lived to at least 50 years old. The Cretaceous rocks, where the crocodiles were found, are about 110 million years old and were deposited on the shores of an inland sea in a tropical environment in central Niger-now part of the Tenere Desert, which is a large section of the Sahara Desert.

Larsson said S. imperator is not a direct ancestor of modern crocodiles, but it is a close cousin. It most resembles the endangered Gharial crocodiles, which are found in India. The distinguishing feature of both the modern Gharial and the S. imperator is a rounded mass of flesh at the tip of the long snout that is used for vocalization. Gharial crocodiles are also the most primitive modern crocodiles. The largest modern crocodiles include the salt-water crocodile and Gharial, which have been recorded up to 24 feet in length.

The team's expeditions in Africa have also recovered numerous new dinosaur finds in Morocco and older rocks in Niger.

Other researchers on the study include Christian A. Sidor of the New York College of Osteopathic Medicine and Boubacar Gado of the Institut pour Recherche et Science Humaine, Niamey, Republic of Niger.

A study from the Massachusetts General Hospital (MGH) supports previous reports that adolescents with bipolar disorder are at increased risk for smoking and substance abuse. The article appearing in the June Drug and Alcohol Dependence -- describing the largest such investigation to date and the first to include a control group -- also indicates that bipolar-associated risk is independent of the risk conferred by other disorders affecting study participants.

"This work confirms that bipolar disorder (BPD) in adolescents is a huge risk factor for smoking and substance abuse, as big a risk factor as is juvenile delinquency," says Timothy Wilens, MD, director of Substance Abuse Services in MGH Pediatric Psychopharmacology, who led the study. "It indicates both that young people with BPD need to carefully be screened for smoking and for substance use and abuse and that adolescents known to abuse drugs and alcohol -- especially those who binge use -- should also be assessed for BPD."

It has been estimated that up to 20 percent of children and adolescents treated for psychiatric problems have bipolar disorder, and there is evidence that pediatric and adolescent BPD may have features, such as particularly frequent and dramatic mood swings, not found in the adult form of the disorder. While elevated levels of smoking and substance abuse previously have been reported in young and adult BPD patients, it has not been clear how the use and abuse of substances relates to the presence of BPD or whether any increased risk could be attributed to co-existing conditions such as attention-deficit hyperactivity disorder (ADHD), conduct disorder or anxiety disorders.

The current study analyzes extensive data -- including family histories, information from primary care physicians, and a detailed psychiatric interview -- gathered at the outset of a continuing investigation following a group of young BPD patients into adulthood. In addition to 105 participants with diagnosed BPD, who enrolled at an average age of 14, the study includes 98 control participants of the same age, carefully screened to rule out mood disorders.

Incidence of each measure -- alcohol abuse or dependence, drug abuse or dependence, and smoking -- was significantly higher in participants with BPD than in the control group. Overall, rates of substance use/abuse were 34 percent in the bipolar group and 4 percent in controls. When adjusted to account for co-occurring behavioral and psychiatric conditions, the results still indicated significantly higher risk in the bipolar group. Analyzing how the onset of bipolar symptoms related to when substance abuse began, revealed that BPD came first in most study participants.

The data also indicated that bipolar youth whose symptoms began in adolescence were more likely to abuse drugs and alcohol than were those whose symptoms began in childhood. "It could be that the onset of mood dysregulation in adolescence puts kids at even higher risk for poor judgement and self-medication of their symptoms," Wilens says. "It also could be that some genetic switch activated in adolescence turns on both BPD and substance abuse in these youngsters. That's something that we are currently investigating in genetic and neuroimaging studies of this group."

He adds that clarifying whether bipolar disorder begins before substance abuse starts could have "a huge impact. If BPD usually precedes substance abuse, there may be intervention points where we could reduce its influence on drug and alcohol abuse. Aggressive treatment of BPD could cut the risk of substance abuse, just as we have shown it does in ADHD." Wilens is an associate professor of Psychiatry at Harvard Medical School.

The National Institute of Mental Health is supporting the long-term study of bipolar youth of which this report is one phase. Co-authors of the Drug and Alcohol Dependence article are Joseph Biederman, MD, Joel Adamson, Aude Henin, Stephanie Sgambati, Robert Sawtelle, Alison Santry and Michael Monuteaux, ScD, MGH Pediatric Psychopharmacology; and Martin Gignac, MD, University of Montreal.

For the first time, researchers have shown that the pre-hatching calls of baby Nile crocodiles actually mean something to their siblings and to their mothers. The calls—which are perfectly audible to humans and sound like "umph! umph! umph!"—tell the others in the nest that it's time to hatch, according to the report in the June 23rd issue of Current Biology, a Cell Press publication. Those cries also tell the mother croc to start digging up the nest.

The new findings, made from a series of "playback" experiments, confirm what had only been suspected on the basis of prior anecdotal observation, according to the researchers Amélie Vergne and Nicolas Mathevon of Université Jean Monnet in France.

The researchers said that the calling behavior is probably critical to the early survival of the young crocodiles.

Although it has not yet been clearly shown, "We can well suppose that hatching synchrony can be of vital importance for crocodiles," Mathevon said. "Indeed, most mortality occurs early in life and hatching vocalizations might well attract predators. Therefore, adult presence at the nest and its response to juvenile vocalizations may offer protection against potential predators. In this sense, it is important for all embryos in the nest to be ready for hatching at the same time so that they all receive adult care and protection."

Crocodilians were known to make sounds within the egg shortly before hatching, the researchers said. To find out what those calls might mean in the new study, the researchers divided crocodile eggs that were due to hatch within 10 days into three groups. One of those groups was played recordings of pre-hatching calls, one was played recordings of noise, and the last was left in silence until they hatched.

The eggs played the pre-hatch sounds more often answered back, they report. Many of the eggs in that group also moved. Finally, all of the eggs in the pre-hatch group hatched during the playback or within 10 minutes of it. Only once did the eggs hearing noise hatch, and the rest hatched at least five hours after the last test.

The researchers then tested the mothers' responses to the calls. "In the zoo where we did the experiments, eggs are removed [from the nest] within a few days following the laying date," the researchers explained. "In spite of this, females continue to guard the nest."

At the end of the incubation period, the researchers hid a loudspeaker underground near the empty nest. They then played pre-hatching calls interspersed with noise to ten mothers. The adults more often turned their heads or moved after egg sounds than after noise, they showed, and eight of the mothers responded to the recorded calls by digging.

The behavior may have a long history, the researchers said.

"As birds also produce embryonic vocalizations that induce parental care, such acoustic communication at an early stage of development may be a shared behavioral feature of past and present Archosaurs," an ancient group of reptiles now represented by modern birds and crocodiles.

Thursday, June 26, 2008

Though the slow moving purple sea urchin may look oblivious, lacking a head, eyes and ears, this prickly creature has an impressive suite of sensory receptors to detect outside signals. And don't overlook this animal's self-defense abilities: it has much more ammunition to activate its innate immune system than humans have. The starlet sea anemone lives in coastal areas that face increasing pollution, and it is better equipped than many land, ocean, and freshwater animals to tolerate environmental stress.

The interior of the brood chamber of a sponge, Amphimedon queenslandica, showing embryos in the early phases of development.

These insights into the biology of marine organisms didn't come from observational studies; they were revealed by deciphering and comparing the animals' genomes. The powerful advantages of using gene catalogs to infer biological function in marine animals are highlighted in a virtual symposium in the June issue of The Biological Bulletin, published by the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts.

Emerging research on the genomic structure of marine organisms is giving scientists new clues as to how certain physiological systems evolved. The genomes of ancient Cnidarians, of which the jellyfish is best known, are being used to discern how cells adhere to form organs and organisms. The genome of Ridgeia piscesae, a tubeworm that has co-evolved with bacteria to thrive in the extreme environment of deep-sea hydrothermal vents, is illuminating the molecular underpinnings of symbiosis.

Genetic sequencing, a once-expensive technology, continues to enjoy reductions in cost and increases in speed that allow even smaller laboratories to produce molecular "maps" to study and compare organisms.

"Science runs on three things – very bright ideas, improved technology and the money to do the research," says R. Andrew Cameron of the California Institute of Technology, who organized The Biological Bulletin virtual symposium along with Jonathan P. Rast of the University of Toronto. "As genomes become less and less expensive to sequence, then it is easier to justify sequencing more genomes to open new areas of study."

By plugging DNA sequences from a marine organism like the sea urchin into a genetic database, researchers can find similarities between sea urchin genes of an unknown function with, for example, human proteins used for sensing light. Further experiments can then test if the sea urchin genes are coding for a sensory protein. Comparing the human and the sea urchin genes can also help illuminate how the sensory protein evolved.

"The benefit of having new model systems is that we can ask questions with organisms in which peculiar characteristics of the genome are very important," Cameron says. For example, some of the marine animals featured in this virtual symposium have unexpectedly complicated sensory systems or immune systems that differ greatly from those of the fruit fly or the nematode worm, standard models in genetic studies. "I think there is good justification for these marine metazoan studies in that we will eventually apply this knowledge to the organism we're most interested in – ourselves," he says.

Prominent investigators who have established genome projects on marine metazoans are participating in The Biological Bulletin virtual symposium. Their papers include:

"All of the people who are represented in this symposium are investigators at the MBL or have used the MBL in one way or another to collect their experimental animals and study them," Cameron says. "MBL has been the focus of new kinds of research for a long time. This symposium is not a gathering of many distant lines of facts; rather it reflects contemporary research within the MBL community."

Viruses can travel around cells they infect by hitching a ride on a microscopic transport system, according to new research. Cells are exposed to foreign DNA and RNA and it is understood that some of this genetic material can be integrated into the host genome. Using modern microscopic techniques, scientists have been able to see how virus DNA is transported in the cell.

Professor Dr Urs Greber from the University of Zurich will describe interactions between viruses and the cell cytoskeleton today (Tuesday 24 June 2008) at the new SGM-RMS satellite meeting, part of the prestigious MICROSCIENCE 2008 conference being held this week at the ExCeL conference centre in London.

"We have been using human adenoviruses (Ads) to investigate transport processes of foreign DNA in the cytoplasm of human cells," said Professor Dr Greber. "Adenoviruses are a diverse family of agents that replicate their DNA genome in the cell nucleus. We wanted to find out how the virus gets to the nucleus to replicate. To do this we have been using live cell fluorescence microscopy, which means we can literally watch the virus travelling inside the cell."

Human adenoviruses can cause respiratory, urinary and digestive infections. They occasionally cause epidemic conjunctivitis, and can be fatal in immunocompromised patients. Adenoviruses can aggravate asthmatic conditions, and are associated with deadly gastroenteritis in babies. This research improves our knowledge of how the virus replicates in host cells.

"Virus DNA is transported from the edge of the cell to the nucleus in the middle by attaching to microtubules. These are microscopic tubes that form part of the cytoskeleton, keeping the cell in shape and carrying molecules around in the cytoplasm," said Professor Dr Greber. "We found an unexpected new link between microtubule-based transport in the cytoplasm of the cell and the import of virus DNA to the nucleus."

Other talks at the one-day SGM meeting will concentrate on the 'tussle' that takes place when a host cell tries to fight back against an invading pathogen. Sir David King will start the day by talking about the 'Twenty first century challenges of sustainability and wellbeing'. Professor Timo Hyypia (University of Turku) will speak on 'Cellular interactions of enteroviruses' and Dr Mark Jepson (University of Bristol) will look at the way in which bacteria invade cells. The manipulation of cellular compartments by the SARS coronavirus for replication purposes will also be discussed by Dr Marjolein Kikkert (Leiden University Medical Centre).

Scientists at the Smithsonian's National Zoo detected a secondary rise in urinary progestin levels in the Zoo's female giant panda Mei Xiang (may-SHONG) earlier this month. The results from the test on Thursday, June 19 lead scientists to believe the hormone rise indicates that it would be mid- to late-July before Mei Xiang either gives birth to a cub or comes to the end of a pseudopregnancy, or false pregnancy, which is common in giant pandas.

Zoo scientists artificially inseminated Mei Xiang with semen from the Zoo's male giant panda Tian Tian (t-YEN t-YEN) March 19. Since then, scientists have conducted weekly hormonal analyses on daily urine samples from Mei Xiang. Zoo veterinarians are conducting weekly ultrasounds on Mei Xiang to monitor any changes in her reproductive tract and look for evidence of a fetus. So far, they have not seen evidence of one.

Because panda fetuses do not start developing until the last weeks of a gestation period, Zoo veterinarians say they do not yet expect to see a fetus. They stress, however, that it is still too early to determine if Mei Xiang is actually pregnant or experiencing a pseudopregnancy.

In 2005, in the last weeks leading up to the birth of Mei Xiang's only cub Tai Shan, she would not cooperate for her weekly ultrasounds and it was not possible to definitively determine if she was pregnant.

This is the sixth year the National Zoo has tried to breed the giant pandas; Mei Xiang had pseudopregnancies in 2002, 2003, 2004 and 2007. She gave birth to Tai Shan in 2005 and did not reproduce in 2006. Mei Xiang, 8 years old, and Tian Tian, 9 years old, live at the Fujifilm Giant Panda Habitat at the National Zoo.

Scientists have long questioned whether the abundant amounts of amyloid plaques found in the brains of patients with Alzheimer's actually caused the neurological disease or were a by-product of its progress. Now, using new research techniques, scientists have shown that a two-molecule aggregate (or dimer) of beta-amyloid protein fragments may play a role in initiating the disease.

Alzheimer's disease is marked by the build-up of plaques consisting of beta-amyloid protein fragments, as well as abnormal tangles of tau protein found inside brain cells. Early in the disease, Alzheimer's pathology is first observed in the hippocampus, the part of the brain important to memory, and gradually spreads to the cerebral cortex, the outer layer of the brain.

In this study, in which the Harvard and Brigham team collaborated with other Harvard researchers and scientists at University College Dublin, Beaumont Hospital and Royal College of Surgeons Ireland, and Trinity College Dublin, Ireland, researchers tested cerebral cortex extracts from brains donated for autopsy by people aged 65 and older with Alzheimer's and other dementias, as well as those without dementia. The extracts contained soluble one-molecule (monomer), two-molecule (dimer), three-molecule (trimer) or larger aggregates of beta-amyloid, as well as insoluble plaque cores. The researchers then injected the extracts into normal rats or added the extracts to slices of normal mouse hippocampus.

Selkoe, lead author Ganesh M. Shankar and colleagues discovered that both the soluble monomers and the insoluble plaque cores had no detectable effect on the hyppocampal slices. However, the soluble dimers induced certain key characteristics of Alzheimer's in the rats. The dimers impaired memory function, specifically the memories of newly learned behaviors.

In the mouse hippocampal slices, the dimers also reduced by 47 percent the density of the dendrite spines that receive messages sent by other brain cells. The dimers seemed to be directly acting on synapses, the connections between neurons that are essential for communication between them.

To confirm this effect, the researchers then injected certain antibodies against beta-amyloid protein fragments. These latched onto and inactivated the dimers, preventing their toxic effects in the animal models. However, much work remains to be done before inactivation of dimers could move into the clinic.

"Scientists have theorized for many years that soluble beta-amyloid may be critical to the development and progression of this devastating disease. Now these researchers have isolated a candidate causative agent from brains of people with typical Alzheimer's and directly tested it in an animal model," said Richard J. Hodes, M.D., Director of the National Institute on Aging(NIA), which financed the research. "While more research is needed to replicate and extend these findings," Hodes said, "this study has put yet one more piece into place in the puzzle that is Alzheimer's."

The animal findings were consistent with what the researchers found when they examined the brain tissues of people who had been clinically diagnosed with Alzheimer's and those without dementia. They detected soluble dimers and some trimers of amyloid in the brains of patients with Alzheimer's, but none or very low levels in those free of the disorder. Some people free of the disorder, however, did have insoluble amyloid plaques in their brains.

"These findings may help explain why people with normal cognitive function are sometimes found to have large amounts of amyloid plaques in their brains, which has been a puzzle for some time," said Marcelle Morrison-Bogorad, director of the NIA Division of Neuroscience. "Their findings noted that the brain of an individual who was never clinically diagnosed with dementia was found with abundant insoluble Alzheimer's plaques, but no soluble beta-amyloid."

Selkoe and Shankar noted that further insights into the early stages of this disease process may answer questions not only about Alzheimer's, but also about age-related memory impairments. "The approaches we used to isolate dimers and the widespread availability of tissues from brain banks, open new avenues of investigation into how these aggregates induce Alzheimer's disease," said Selkoe. "We still need to find out why dimers in particular are so destructive to neurons."

Close-up of the foot of a living Trichobatrachus robustusshowing the white bony claws protruding from the tips of the toes.(Credit: David C. Blackburn)

Biologists at Harvard University have determined that some African frogs carry concealed weapons: When threatened, these species puncture their own skin with sharp bones in their toes, using the bones as claws capable of wounding predators.

The unusual defense mechanism is described by Harvard's David C. Blackburn, James Hanken, and Farish A. Jenkins, Jr., in a forthcoming issue of the journal Biology Letters.

"It's surprising enough to find a frog with claws," says Blackburn, a doctoral student in Harvard's Department of Organismic and Evolutionary Biology. "The fact that those claws work by cutting through the skin of the frogs' feet is even more astonishing. These are the only vertebrate claws known to pierce their way to functionality."

"Most vertebrates do a much better job of keeping their skeletons inside," he adds.

Blackburn first became aware of the clawed frogs while conducting fieldwork in the central African nation of Cameroon. When he picked up one of the hulking fist-sized frogs, it flailed its hind legs violently, scratching him and drawing blood.

Back in the U.S., Blackburn examined museum specimens of 63 African frog species. He noticed that in 11 species -- all in the genera Astylosternus, Trichobatracus, and Scotobleps and all native to central Africa -- the bones at the ends of the toes were pointed and hooked, with smaller, free-floating bones at their tips. Eventually he determined that these small nodules at the tips of the frogs' feet were connected to the rest of the toe by a collagen-rich sheath.

"These nodules are also closely connected to the surrounding skin by dense networks of collagen," Blackburn says. "It appears they hold the skin in place relative to these claw-like bones, such that when the frog flexes a certain muscle in the foot, the sharp bone separates from the nodule and bursts through the skin."

This claw-like structure is no conventional claw, though: It is pure bone, free of the keratin sheath that normally surrounds vertebrate claws. And unlike a claw that retracts into a specialized structure in an animal's foot, as in cats, the site where the frogs' foot bones emerge appears to be covered with ordinary skin.

While these frogs were mentioned in the scientific literature on a few occasions from 1900 to 1925, they are generally little-known in the U.S., appearing in few museum collections. Even the handful of researchers who wrote about them a century ago often misinterpreted the piercing of the skin as damage incurred during preservation of specimens.

The frogs are widely roasted and eaten in Cameroon, where hunters -- evidently well aware of the risk of injury -- go to great lengths to avoid handling them when alive.

"Cameroonian hunters will use long spears or machetes to avoid touching these frogs," Blackburn says. "Some have even reported shooting the frogs."

Of more than 5,500 known frog species, Blackburn and his colleagues found just 11 with claws, and speculate there may be another couple of similarly equipped species.

Blackburn plans to study live specimens of the African frogs to determine whether retraction of the foot bones back into the body is an active or a passive process, and how the damaged skin regenerates after the claws are deployed.

"We suspect, since the frog does suffer a fairly traumatic wound, that they probably use these claws infrequently, and only when threatened," Blackburn says.

Blackburn, Hanken, and Jenkins' work was funded by the National Science Foundation's AmphibiaTree project and by a Putnam Expeditionary Grant from Harvard's Museum of Comparative Zoology.

A new study by the Bronx Zoo-based Wildlife Conservation Society found that jack rabbits living in the Greater Yellowstone Ecosystem have apparently hopped into oblivion. The study, which appears in the journal Oryx, also speculates that the disappearance of jack rabbits may be having region-wide impacts on a variety of other prey species and their predators.

According to the study, historical records from more than 130 years ago indicate that white-tailed jack rabbits were once locally abundant in Greater Yellowstone, a 60,000 square kilometer (23,166 square mile) ecosystem that contains both Grand Teton and Yellowstone National Parks. However, the WCS study found that no jack rabbit sightings could be confirmed in Yellowstone since 1991 and only three in Grand Teton since 1978.

No one knows what caused the rabbits to disappear, according to the study's lead author, Dr. Joel Berger, a Wildlife Conservation Society conservationist, and professor at the University of Montana. "It could be disease, extreme weather, predation or other factors," Dr. Berger said. "Since the rabbits blipped off without knowledge, there has simply been no way to get at the underlying cause."

Dr. Berger believes that the absence of jack rabbits -- historically important prey species in the Greater Yellowstone Ecosystem -- may be causing elevated predation by coyotes on juvenile elk, pronghorn and other ungulates. Elsewhere, when rabbit densities drop predators often turn to preying more on livestock, according to the study. But without baseline data on rabbit numbers in Greater Yellowstone, assessing the impacts of predators such as grey wolves, which were reintroduced in 1995, becomes more difficult.

"Lacking a sense of historical conditions, it will always be difficult to decide whether current systems function ecologically like past ones," said Dr. Berger.

Berger goes on to suggest that wildlife managers should consider reintroduction of white-tailed jack rabbits into Grand Teton and Yellowstone National Parks. "Reintroduction may result in the establishment of dynamic ecological processes that were intact before rabbits vanished from the ecosystem," Dr. Berger said. "From the perspective of ecological health and wildlife conservation, reintroduction would also show that species loss has serious ecological costs."

The Wildlife Conservation Society works to save wildlife in and around the Greater Yellowstone Ecosystem, and uses science to identify key wildlife corridors and migration routes.

Monday, June 23, 2008

While rabbits continue to ravage Australia’s native landscapes, rabbit fish may help save large areas of the Great Barrier Reef from destruction.

The reason, say scientists, is the same in both cases – both rabbits and rabbit fish are efficient herbivores, capable of stripping an area of vegetation. However, in the case of the Reef, it is the vegetation that is the problem – and the rabbit fish, the answer.

“When a coral reef is weakened or damaged through human activity such as climate change or pollution or by a natural disaster like a cyclone, the coral will usually recover provided it is not choked by fast-growing marine algae,” explains Professor David Bellwood of the ARC Centre of Excellence for Coral Reef Studies and James Cook University.

“The problem is that over the years we have fished down the populations of fish that normally feed on the young weed to such a degree that the weed is no longer kept in check, it can now smother the young corals and take over. This is called a phase-shift, and the chances of corals re-establishing afterwards are usually poor. If the weed takes over, you’ve lost your reef.”

Prof. Bellwood and fellow researcher Rebecca Fox have spent recent years running live experiments to see what happens when a reef turns to weed – and which fish, if any, are of help in restoring the coral.

“To our surprise and disappointment, the fish that usually ‘mow’ the reef – parrot fishes and surgeon fish - were of little help when it came to suppressing well established weedy growth. Most herbivores simply avoided the big weeds.

“Then, to our even greater surprise a fish we had never seen in this area before was observed grazing on the weed. The rabbit fish (Siganus canaliculatus), came out of nowhere and began to clear-fell the weed placed on the reef crest.”

The rabbit fish were caught on underwater videocams, in schools of up to 15 fish, grazing the crest, slopes and outer flats of the reef, and chomping away at more than ten times the rate of other weed-eaters.

“The rabbit fish is not a fish you tend to take a lot of notice of,” Prof. Bellwood explains. “Like its terrestrial counterpart, it is brown, bland and easily overlooked – but it could be very important when it comes to protecting the GBR.”

“We hadn’t seen it previously at this site despite conducting over 100 visual censuses. This made its appearance in numbers sufficient to check the weedy growth all the more remarkable.”

However the team noticed the rabbit fish concentrated their weed-removal efforts on the crest of the reef and were less effective on the slopes and flats – a feeding preference that is yet to be explained.

In a previous study, an overgrown reef had been cleaned up by another unexpected intruder, a striped batfish.

Ms. Fox explained that the recovery of damaged reefs may depend on several different ‘guilds’ of fishes, with different feeding preferences, that will focus on particular parts of the reef and stages of the weed infestation.

For such an approach to work, however, all the various species have to be kept intact in the reef environment, ready to play their part in a salvage operation when it becomes necessary.

“In Australia these herbivore fish populations are still in fairly good shape, but around the world as the big predators are fished out, local fishermen are targetting the herbivores. In Hawaii, the Caribbean, Indonesia, Micronesia and French Polynesia there are reports of serious declines in herbivore numbers of up to 90 per cent.

“By killing them, we may be unwittingly eliminating the very thing which enables coral reefs to bounce back from the sort of shocks which human activity exposes them to.”

Prof. Bellwood says that one of the lessons from the video study is that obscure fish species may play a critical role in the survival and maintenance of coral ecosystems, and should not be overlooked. They are a key part of the resilience of the whole reef system.

“On land the rabbit is a major headache, but in the sea the rabbit fish may be an important factor in helping to keep the world’s number one tourist attraction in good shape,” he says.

New research led by Dr Melanie Massaro and Dr Jim Briskie at the University of Canterbury, which found that the New Zealand bellbird is capable of changing its nesting behaviour to protect itself from predators, could be good news for island birds around the world at risk of extinction.

The introduction of predatory mammals such as rats, cats and stoats to oceanic islands has led to the extinction of many endemic island birds, and exotic predators continue to threaten the survival of 25 percent of all endangered bird species worldwide.

Dr Massaro says the impact of exotic predators on the native birds of oceanic islands is particularly profound as they evolved over millions of years largely in the absence of these predators and appear naïve towards newly introduced mammals.

But their study on the bellbird, an endemic New Zealand bird, has identified the ability of a previously naïve island bird to change its nesting behaviour in response to the introduction of a large suite of exotic mammalian predators by humans.

Bellbirds were studied at three sites with varying levels of predation risk: a mainland site with exotic predators present (high risk); a mainland site with exotic predators experimentally removed (recent low risk); and an offshore island where exotic predators have never been introduced (permanent low risk).

It was found that females spent more time on the nest per incubating bout with increased risk of predation, a strategy that minimised activity at the nest and decreased the risk of an exotic predator locating and destroying the eggs.

"Parental activity during the nestling period, measured as number of feeding visits per hour, also decreased with increasing nest predation risk across sites, which would further reduce the risk of an exotic predator destroying the nest," Dr Massaro said.

"It shows that such species are not necessarily trapped by their evolutionary history as is generally considered to be the case but they, in fact, have the ability to change their behaviours in ways that appear adaptive.

"More importantly, this study demonstrates that such a change can occur over an ecologically relevant time-scale of years and not centuries."

Drs Massaro and Briskie say although their research was done on New Zealand birds, the conclusions are applicable worldwide. They believe conservation efforts towards the survival of other island birds could be more effective if advantage was taken of the ability of island birds to respond to exotic predators, especially when the elimination of such predators is not possible.

Sunday, June 22, 2008

Nearly a month after China's devastating earthquake, the Wolong Nature Reserve held a funeral Tuesday for a Panda that was crushed in the temblor. The world famous panda center was badly damaged by the May 12 quake. Officials initially thought all the Pandas had survived and only later discovered that several were missing.

The Ceremony

Nine-year-old Mao Mao, the mother of five at the breeding center, was found Monday, her body crushed by a wall of her enclosure when the river behind it swelled with landslide debris.

On Tuesday, panda keepers and other workers placed her remains in a small wooden crate and wheeled her quietly to a patch of ground outside the breeding center where a freshly dug hole waited.

The center's director, Zhang Hemin, stood with his cap in hand and then shoveled in a few spades of dirt.

Mao Mao's keeper, He Changgui, stepped forward, crying, and placed two apples and a piece of bread by the covered grave. There were three minutes of silence.

As the others left, the director of the U.S.-based Pandas International, Suzanne Braden put her arm around He.

"You must look after her babies, OK?" she said. "And their babies."

He nodded. "I will go back to see her everyday," he said.

After the Quake

The endangered panda is revered as a kind of national mascot in China. About 1,590 pandas live in the wild, mostly in Sichuan and the neighboring province of Shaanxi. Another 180 have been bred in captivity. The nature reserve was heavily damaged by the quake, which was centered just 20 miles (30 kilometers) away in the heart of Sichuan province's mountainous panda country.

Five Wolong staff members were killed in the quake. Most staffers, tourists and pandas were outside at the time.

Nearly 70,000 people were killed, and more than 5 million were left homeless by the 7.9-magnitude quake.

Wolong

Some of Wolong's pandas have been moved to another breeding center in Sichuan's provincial capital, Chengdu, and eight were flown to Beijing for a previously scheduled six-month stay at the Beijing Zoo for the Olympics.

The center will have to be relocated to a new site because of safety issues, said Huang Yan, deputy director of research, but it will remain within the confines of Wolong Nature Reserve, which is located in a damp, narrow valley several hours' drive from Chengdu.

He, Mao Mao's keeper, returned from the grave with red eyes. He had been the panda's only keeper since she was three years old. He would speak to her in the local Sichuan dialect as he worked.

"It's like you could say something and she would understand," he said. "If you were happy, she was happy too."

Saturday, June 21, 2008

Woolly mammoths, giant armadillos and three species of camels were among more than 30 mammals that were hunted to extinction by North American humans 13,000 to 12,000 years ago, according to the most realistic, sophisticated computer model to date. The news is reported in the June 8 issue of the journal Science.

John Alroy, a researcher with the National Center for Ecological Analysis and Synthesis (NCEAS) at the University of California, Santa Barbara, performed the modeling and is the single author of the paper. NCEAS houses the best ecosystem computer modeling capacity available, according to Alroy.

“This was a big event in North America,” said Alroy. “And, although humans were responsible for the extinctions, it wasn’t clear to them because it happened over a 1,000 year period. It took so long that they didn’t realize it until it was too late.”

“More than half of the large mammal biota of the Americas disappeared in a cataclysmic extinction wave at the very end of the Pleistocene,” begins Alroy in the Science article. Some of the mammals that became extinct are:

* woolly mammoths

* Columbian mammoths

* American mastodons

* three types of ground sloths

* glyptodonts

* giant armadillos

* several species of horses

* four species of pronghorn antelopes

* three species of camels

* giant deer

* several species of oxen

* giant bison

Earlier computer simulations were too simple to grasp the total picture of extinctions, according to Alroy. He said the current model is a conservative one that is quite robust to criticism.

But why did some species of large mammals become extinct and others not? Moose, Canadian elk and bison survived. “These had a broader distribution,” explained Alroy. They were able to move into what is now Canada as the glaciers melted. “These animals may also have developed more ways to avoid humans since they co-evolved with humans here, in Europe and Asia,” he said.

Understanding the mechanisms that drive healthy immune responses is important when it comes to combating autoimmune diseases, which occur when cells that should attack invading organisms turn on the body instead. In a study published in the June 13, 2008, issue of Immunity, Tufts researcher Stephen Bunnell, PhD, describes how cell surface receptors cooperate to generate immune responses in a process referred to as costimulation. To reveal how these receptors communicate, Bunnell, assistant professor of pathology at Tufts University School of Medicine and a member of the immunology program faculty at the Sackler School of Graduate Biomedical Sciences, formulated a fluorescent imaging technique that reveals the dynamic movements of proteins within living T cells.

T cells play an essential role defending the body against viruses and bacteria. To mount these defenses, T cells must sense these pathogens via cell surface receptors known as antigen receptors. T cells are much more likely to 'see' the invading organisms when a second group of proteins, known as integrins, becomes involved. Integrins are also cell surface receptors, and act as adhesive hooks that allow the T cell to latch onto its environment. "What we are providing here is insight into how these receptors collaborate, or 'talk' to one another," says Bunnell.

First author Ken Nguyen, a graduate student in immunology in Bunnell's laboratory, found that a particular integrin, VLA-4, influences how cellular structures known as SLP-76 microclusters move within the responding T cell. These structures, which were first discovered by Bunnell, are assembled by the antigen receptor and relay information that is essential for T cell activation. "SLP-76 is a molecular building block that is employed by both antigen receptors and integrins. When VLA-4 is not involved, SLP-76 microclusters move away from the antigen receptor, which causes them to fall apart. We discovered that VLA-4 prevents the separation of SLP-76 microclusters from the antigen receptor. This keeps each SLP-76 microcluster intact for a longer time, and favors the transmission of stimulatory signals," says Bunnell.

Actin filaments are a major component of the 'skeleton' that enables cells to move. In activated T cells, many actin filaments grow at one end and fall apart at the other. These actin filaments 'flow' away from the growing end, much like a treadmill. Nguyen and colleagues showed that these flows drive SLP 76 from the antigen receptor, but are slowed when VLA-4 is engaged. "By altering the movement of actin within the cell, the integrin is collaborating with the antigen receptor to immobilize these complexes and make them survive over time," says Bunnell.

"We have known for some time that integrin signaling and T cell costimulation contribute to autoimmunity. Bunnell's images allow us to see that these can be related phenomena: integrins sensitize the immune system to antigens," says Naomi Rosenberg, PhD, dean of the Sackler School of Graduate Biomedical Sciences and vice dean for research at Tufts University School of Medicine.

In previous research, integrins and antigen receptors were thought of as working individually, in terms of geography and mechanism. Earlier studies by Bunnell, and recent studies by other investigators, have led researchers to believe that antigen receptors are most effective when located near integrins. Importantly, this study indicates that integrins influence the transmission of signals through the same complexes used by the T cell antigen receptor.

"You need to understand the communication between the receptors in order to intelligently intervene and enhance the response to a virus or bacteria, or inhibit a destructive response," says Bunnell.

Bunnell's future research will examine how integrins alter the mechanical properties of activated T cells. By studying how integrins influence the SLP-76 complex, Bunnell will gain insights into the costimulatory processes that enable normal immune responses, and go awry in autoimmune diseases.